生物谷報(bào)道：T4病毒的DNA需要在特定“分子馬達(dá)”（molecular motor）的幫助下才能進(jìn)入病毒的衣殼,。Purdue大學(xué)和美國(guó)Catholic大學(xué)的研究人員最近發(fā)現(xiàn)了一種在運(yùn)轉(zhuǎn)這種發(fā)動(dòng)機(jī)中發(fā)揮重要作用的酶——ATPase的結(jié)構(gòu),。文章第一作者為Purdue大學(xué)科學(xué)院Michael Rossmann實(shí)驗(yàn)室博士后孫斯陽(yáng)（Siyang Sun，音譯）,。詳細(xì)研究?jī)?nèi)容刊登于3月22日《Molecular Cell》,。
這種發(fā)動(dòng)機(jī)在其它病毒中也存在，包括人皰疹病毒,。“這是首次對(duì)與DNA包裝發(fā)動(dòng)有關(guān)的ATPase的結(jié)構(gòu)進(jìn)行測(cè)定,，”Rossmann教授說，“病毒首先組裝蛋白頭部的蛋白殼,，然后將DNA裝入空的衣殼中,。這種過程可以比喻為建造房屋，然后添加家具,。”
DNA記錄了病毒的全部特征,，衣殼保護(hù)了這種記錄，確保病毒能夠通過感染宿主不斷繁殖,。ATPase將ATP降解為ADP時(shí),，產(chǎn)生運(yùn)轉(zhuǎn)包裝發(fā)動(dòng)機(jī)所需的能量。ATPase特意破壞磷酸鹽和ADP之間的化學(xué)鍵,。
研究人員通過將運(yùn)轉(zhuǎn)T4病毒的分子馬達(dá)所需的ATPase的結(jié)構(gòu)與解旋酶（helicases）的結(jié)構(gòu)進(jìn)行對(duì)比,，推測(cè)了一種可能的馬達(dá)工作機(jī)制。解旋酶是在基因復(fù)制過程中將雙鏈DNA分開為單鏈的酶,。DNA復(fù)制過程中,，解旋酶選擇性結(jié)合或脫離DNA，如尺蠖一樣沿螺旋移動(dòng)將雙鏈分為單鏈,。研究人員推測(cè)馬達(dá)利用相似的尺蠖機(jī)制將DNA擠入病毒中,。
研究人員利用X射線結(jié)晶學(xué)技術(shù)分析了ATPase的結(jié)構(gòu)。皰疹和其他病毒也許含有相似的DNA包裹馬達(dá),，這項(xiàng)發(fā)現(xiàn)為設(shè)計(jì)干擾這些馬達(dá)的藥物,、治療病毒感染,、發(fā)展微型“納米馬達(dá)”提供了參考。
“現(xiàn)在談?wù)撨@些發(fā)現(xiàn)的潛在應(yīng)用價(jià)值為時(shí)尚早,，” Rossmann說,，“希臘人發(fā)現(xiàn)行星時(shí)，他們一定不會(huì)想到那些發(fā)現(xiàn)導(dǎo)致了幾百個(gè)世紀(jì)后的航天軌道（spacecraft trajectories）設(shè)計(jì),。”該研究主要受美國(guó)國(guó)家科學(xué)基金會(huì)和人類前沿科學(xué)計(jì)劃組織（Human Frontier Science Program）資助,。
部分英文原文：
Copyright © 2007 Cell Press. All rights reserved.
Molecular Cell, Vol 25, 943-949, 23 March 2007
The Structure of the ATPase that Powers DNA Packaging into Bacteriophage T4 Procapsids
Siyang Sun,1 Kiran Kondabagil,2 Petra M. Gentz,1,3 Michael G. Rossmann,1, and Venigalla B. Rao2,
1 Department of Biological Sciences, Purdue University, 915 W. State Street, West Lafayette, IN 47907, USA
2 Department of Biology, The Catholic University of America, 620 Michigan Avenue NE, Washington, DC 20064, USA
Corresponding author
Michael G. Rossmann
[email protected]
Corresponding author
Venigalla B. Rao
[email protected]
Packaging the viral genome into empty procapsids, an essential event in the life cycle of tailed bacteriophages and some eukaryotic viruses, is a process that shares features with chromosome assembly. Most viral procapsids possess a special vertex containing a dodecameric portal protein that is used for entry and exit of the viral genome. The portal and an ATPase are parts of the genome-packaging machine. The ATPase is required to provide energy for translocation and compaction of the negative charges on the genomic DNA. Here we report the atomic structure of the ATPase component in a phage DNA-packaging machine. The bacteriophage T4 ATPase has the greatest similarity to monomeric helicases, suggesting that the genome is translocated by an inchworm mechanism. The similarity of the packaging machines in the double-stranded DNA (dsDNA) bacteriophage T4 and dsRNA bacteriophage 12 is consistent with the evolution of many virions from a common ancestor.
The T4 DNA-Packaging Machine
(A) A schematic diagram shows the T4 procapsid while being filled with DNA. The portal protein, gp20, forms a dodecameric head-tail connector through which the genome enters the procapsid and exits the mature phage. The stoichiometry of the large terminase gp17 oligomer is suggested to be pentameric or decameric. The amino-terminal domain of gp17 has ATPase activity, whereas the carboxy-terminal domain has nuclease activity. There are probably eight to ten gp16 monomers in the small terminase oligomer. The small terminase functions to enhance the ATPase activity of th
